This proposal requests support for a Keystone Symposia meeting entitled Cell Death Pathways: Beyond Apoptosis, organized by Serge Przedborski and Richard J. Youle, which will be held in Banff, Alberta, Canada from March 19 - 24, 2012. Mounting evidence indicates that cell death in diseases results from complex interactions between molecular mechanisms taking place within the degenerating cells (cell-autonomous) and outside the degenerating cells (non-cell autonomous). At the cross road of these diverse signaling pathways are found the mitochondria which, through proper mitochondrial dynamics and regulated mitochondrial elimination by autophagy (i.e., mitophagy), play a crucial role in maintaining the well-being of the cells. This meeting will focus on the general mechanisms of cell death including the Bcl-2 family and caspase proteases, the role of mitochondrial dynamics and mitophagy, the usefulness of bioinformatics to unravel death-pathways, the contribution of non-cell autonomous mechanisms to cell death, and on therapeutic strategies to protect against cell death. Opportunities for interdisciplinary interactions will be significantly enhanced by the concurrent meeting on Mitochondrial Dynamics and Function, which will share a keynote address and two plenary sessions with this meeting. PUBLIC HEALTH RELEVANCE: In the healthy human adult, more than one million cells die each second to avoid the accumulation of superfluous, ectopic, damaged, aged or mutated cells. Hence, cell death and its regulation are of central importance for biomedical research at many levels: for understanding normal tissue biology and the pathogenesis of numerous diseases, for pharmacological interventions that prevent unwarranted cell death, as well as for the therapeutic destruction of tumor cells. The Keystone Symposia meeting on Cell Death Pathways: Beyond Apoptosis will bring together investigators from many distinct fields in order to facilitate new ideas regarding the means by which cell death can be manipulated for therapeutic purposes.